What is best workflow for having a scene with multiple light setups?
Instead of layers use scenes

In this example I want to have two scenes with the light on different places, so
I created a new scene by pressing the + button for scene on the info window 

then moved the light to the other side and rotated it.



You can  choose to link your objects or do a full copy, is up to you and how you want to use your resources. If you link your objects then changes made in one scene will affect objects on others) 

Then in the compositor I can have each scene as a render layer and switch between the two of them at will.



If you want to save each scene to a different file on the same render operation then just add file output nodes to each of the scenes.